Long-term seizure and psychosocial outcomes of vagus nerve stimulation for intractable epilepsy

Vagus nerve stimulation (VNS) is a widely used adjunctive treatment option for intractable epilepsy. Most studies have demonstrated short-term seizure outcomes, usually for up to 5 years, and thus far, none have reported psychosocial outcomes in adults. We aimed to assess long-term seizure and psychosocial outcomes in patients with intractable epilepsy on VNS therapy for more than 15 years. We identified patients who had VNS implantation for treatment of intractable epilepsy from 1997 to 2013 at our Comprehensive Epilepsy Program and gathered demographics including age at epilepsy onset and VNS implantation, epilepsy type, number of antiepilepsy drugs (AEDs) and seizure frequency before VNS implantation and at the last clinic visit, and the most recent stimulation parameters from electronic medical records (EMR). Phone surveys were conducted by research assistants from May to November 2014 to determine patients' current seizure frequency and psychosocial metrics, including driving, employment status, and use of antidepressants. Seizure outcomes were based on modified Engel classification (I: seizure-free/rare simple partial seizures; II: > 90% seizure reduction (SR), III: 50–90% SR, IV: < 50% SR; classes I to III (> 50% SR) = favorable outcome). A total of 207 patients underwent VNS implantation, 15 of whom were deceased at the time of the phone survey, and 40 had incomplete data for medical abstraction. Of the remaining 152, 90 (59%) were contacted and completed the survey. Of these, 51% were male, with the mean age at epilepsy onset of 9.4 years (range: birth to 60 years). There were 35 (39%) patients with extratemporal epilepsy, 19 (21%) with temporal, 18 (20%) with symptomatic generalized, 5 (6%) with idiopathic generalized, and 13 (14%) with multiple types. Final VNS settings showed 16 (18%) patients with an output current > 2 mA and 14 (16%) with rapid cycling. Of the 80 patients with seizure frequency information, 16 (20%) had a modified Engel class I outcome, 14 (18%) had class II, 24 (30%) had class III, and 26 (33%) had class IV. Eighty percent said having VNS was worthwhile. Among the 90 patients, 43 patients were ≥ 18 years old without developmental delay in whom psychosocial outcomes were further analyzed. There was a decrease in the number of patients driving (31% vs 14%, p = 0.052) and working (44% vs 35%, p = 0.285) and an increase in the number of patients using antidepressant medication (14% vs 28%, p = 0.057) at the time of survey compared to before VNS. In this subset, patients with > 50% SR (60%) were taking significantly fewer AEDs at the time of survey compared to patients with unfavorable outcomes (median: 3 vs 4, p = 0.045). The associations of > 50% SR with the psychosocial outcomes of driving, employment, and antidepressant use were not significant, although 77% of this subset said VNS was worthwhile.This is the first study that assesses both seizure and psychosocial outcomes, and demonstrates favorable seizure outcomes of > 50% SR in 68% of patients and seizure freedom in 20% of patients. A large majority of patients (80%) considered VNS therapy worthwhile regardless of epilepsy type and psychosocial outcomes.     

Attention deficits in children with epilepsy: Preliminary findings

ObjectiveAttention difficulties are a common clinical complaint among children with epilepsy. We aimed to compare a range of attentional abilities between groups of children with two common epilepsy syndromes, Temporal Lobe Epilepsy (TLE) and Idiopathic Generalized Epilepsy (IGE), and to healthy controls. We also investigated whether epilepsy factors (laterality of seizure focus, epilepsy onset, duration, and severity) were related to attentional abilities.MethodsMultiple dimensions of attention (selective, sustained, and divided attention and attentional control) were assessed directly with standardized neuropsychological measures in 101 children aged 6–16 years (23 children with TLE, 20 with IGE and 58 healthy controls). Attention was also assessed indirectly, via a parent-report measure.ResultsChildren with TLE performed worse than children with IGE (p = 0.013) and healthy controls (p < 0.001) on a test of attentional control, but no between-group differences were apparent on tests of other attentional abilities. Compared to healthy controls, greater attention problems were reported by parents of children with TLE (p = 0.006) and IGE (p = 0.012). Left-hemisphere seizure focus and greater epilepsy severity were associated with poorer attentional control and sustained-divided attention, respectively, but no other epilepsy factors were associated with attentional abilities.SignificanceThese findings suggest that children with localization-related epilepsy, but not generalized epilepsy, may be at risk of deficits in attentional control. Interventions aimed at improving attentional control may be targeted at children with localization-related epilepsy, particularly those with a left-hemisphere seizure focus, who appear to be particularly susceptible to this type of attentional deficit.     

Minimal access keyhole surgery for mesial temporal lobe epilepsy

A keyhole surgical approach for the treatment of medically intractable temporal lobe epilepsy is described. Additionally, patients who had keyhole surgery are contrasted with individuals who underwent a non-keyhole approach for outcome parameters of seizure freedom, complications, and speed of recovery. Patients who had a keyhole approach for temporal lobe epilepsy with over 2 years follow-up were compared with all patients who had selective amygdalohippocampectomy performed in a non-keyhole fashion over the same time period. Rates of seizure freedom were comparable in the 17 patients with keyhole surgery and the 34 individuals who had a non-keyhole approach. However, patients treated with keyhole surgery were discharged from the hospital earlier than non-keyhole patients (p = 0.04), and with a shorter operative time (p = 0.0001). The restricted keyhole surgical exposure has not limited the ability to perform surgery for temporal lobe epilepsy with favorable results on reducing the seizure tendency, and patients may be benefited by a minimal access technique with a more rapid recovery from surgery.     

Impact of choice of coping strategies and family functioning on psychosocial function of young people with epilepsy

Both medical and psychological factors have an important impact upon the psychosocial functioning of young people with epilepsy. The purpose of this study was to identify factors that distinguish young people with epilepsy and high psychosocial functioning from those with lower levels. The participants were 114 young people (40 males, 74 females) with active epilepsy and a mean age of 17.92 years (SD = 3.90) who completed either a paper (60.5%) or a web-based survey (39.5%) comprising demographic, medical, and psychosocial measures. Psychosocial measures included family functioning, adolescent coping, anxiety, depression, and quality of life. A latent class analysis produced two psychosocial functioning groups based on participants' scores for anxiety, depression, and quality of life. Young people were more likely to be members of the group with poor psychosocial functioning if they had a seizure in the last month (Wald = 5.63, p < .05), came from families with lower levels of communication and problem solving (Wald = 5.28, p < .05), and made greater use of non-productive (emotion-focused) coping strategies such as wishful thinking, withdrawal, and worry (Wald = 12.00, p < .01). The findings suggest that, in addition to standard medical treatment, clinicians may promote better outcomes by strengthening family functioning and encouraging less use of nonproductive coping strategies.     

Psychosocial factors associated with in postsurgical prognosis of temporal lobe epilepsy related to hippocampal sclerosis

We examined the long-term psychosocial trajectory in a consecutive and homogeneous series of 120 patients followed up for five years after corticoamygdalohippocampectomy (CAH). Evaluation of psychosocial variables at baseline and at five-year follow-up were compared. After five years of CAH, a significant improvement in educational level (p = 0.004) and employment status (p < 0.001) was observed, although retirement (p < 0.001) and divorce (p = 0.021) rates increased. In a long-term follow-up, a tendency to have similar QOL profile was observed between Engel classes IA and IB (p > 0.05). A more favorable surgical outcome (Engel IA) was related to better psychiatric status (p = 0.012). Poor psychosocial adjustment before surgery was the most important predictor of QOL outcome (p < 0.05). Patients' trajectory after surgical treatment showed positive effects mainly in those with better seizure outcome. Our results emphasized the influence regarding baseline psychosocial functioning on postoperative psychosocial adjustment. Furthermore, many psychosocial gains and difficulties after surgery may be similar in developing and developed countries.     

Predictors of intellectual functioning after epilepsy surgery in childhood: The role of socioeconomic status

ObjectiveThe objective of this study was to evaluate the association between socioeconomic status and intellectual functioning in children with medically refractory epilepsy, before and after resective epilepsy surgery. Family environment is a strong contributor to cognitive development in children and has been recently shown to play a significant role in intellectual outcome after surgery in children with epilepsy.MethodsOne hundred children who had undergone resective epilepsy surgery and completed preoperative and postoperative assessments of IQ as part of clinical care were included in the study. We evaluated the impact of epilepsy-related variables, income quintile, and residence location on IQ.ResultsGreater improvements in IQ after surgery were associated with an older age at surgery (β = .235, p = .018). Higher IQ scores at follow-up were associated with an older age of seizure onset (β = .371, p < .001), older age at surgery (β = .356, p < .001), unilobar epileptogenic focus (β = .394, p < .001), and mesial temporal sclerosis (β = .338, p = .001) or tumor (β = .457, p < .001) in comparison with malformation of cortical development; age at seizure onset did not remain as a significant predictor in multivariable regression analysis. Income quintile, residence location, seizure control, and antiepileptic medication use were not significant predictors.ConclusionsEpilepsy-related variables were the strongest predictors of IQ and postoperative change in IQ. We were unable to identify a significant association between IQ and socioeconomic status. Future research should evaluate the impact of multiple aspects of family environment.     

Effect of successful epilepsy surgery on subjective and objective sleep parameters – a prospective study

ObjectiveTo evaluate the effect of surgery on subjective and objective measures of sleep quality among patients with medically refractory focal epilepsy.MethodsIn a prospective cohort study, patients with medically refractory epilepsy undergoing epilepsy surgery were recruited. All patients were assessed seven days pre- and three months post-surgery in terms of history pertaining to epilepsy and sleep, Epworth sleepiness score (ESS), one week sleep log and over night polysomnography (PSG).ResultsAmong 17 patients (mean age 18, 11 males), seizure frequency had reduced (p = 0.04) and self reported sleep parameters had significantly improved (reduced total duration of night time sleep, regularity on one week sleep log and ESS (p < 0.05)) three months following epilepsy surgery. Patients with good surgical outcome (n = 12) showed reduced seizure frequency (p = 0.01) and reduced ESS with corresponding reduction in arousal index (AI) (p = 0.02) and increase in total sleep time (p = 0.03), postoperatively. Three patients in the good surgical outcome group showed reduction in apnea–hypopnea index (AHI) from more than five to less than five. There was no significant change either in seizure frequency, self reported clinical parameters or PSG parameters among patients with poor surgical outcome.ConclusionEpilepsy surgery improves subjective sleep parameters in patients with medically refractory epilepsy during the early post operative period. Successful epilepsy surgery may improve objective (PSG documented) sleep quality, sleep architecture and obstructive sleep apnea with resultant reduction in excessive daytime sleepiness.     

Seizure precipitants in Dravet syndrome: What events and activities are specifically provocative compared with other epilepsies?

ObjectivesThis study aimed to describe seizure precipitants in Dravet syndrome (DS) compared with other epilepsies.MethodsSeizure precipitants as reported in a Dutch cohort of patients with DS with pathogenic SCN1A mutations (n = 71) were compared with those of a cohort with childhood epilepsy (n = 149) and of a community-based cohort with epilepsy (n = 248); for all three Dutch cohorts, the same type of questionnaire was used. Seizure precipitants were categorized as ‘fever’, ‘visual stimuli’, ‘sleep deprivation’, ‘stress, including physical exercise’, ‘auditory stimuli’, and ‘other’.ResultsFor 70 (99%) of 71 patients with DS, at least one seizure precipitant was recalled by parents. Seizure precipitants that were reported in more than half of the cohort with DS were as follows: having a fever (97%), having a cold (68%), taking a bath (61%), having acute moments of stress (58%), and engaging in physical exercise (56%). Seizure precipitants freely recalled by parents were often related to ambient warmth or cold–warmth shifts (41%) and to various visual stimuli (18%).Patients with DS had more positive seizure precipitant categories (median 4) compared with the cohort with childhood epilepsy (median 2) and the community-based cohort with epilepsy (median 0) (p < 0.001) and showed the highest percentage in each category (all p < 0.001). Within the category ‘stress, including physical exercise’, physical exercise was more often reported to provoke seizures in stress-sensitive patients in the cohort with DS than in the cohort with childhood epilepsy (78% vs. 35%, p < 0.001). In the cohort with childhood epilepsy, physical exercise was more often reported in fever-sensitive children than in other children (25% vs. 12%, p = 0.042).ConclusionsOur study shows a high prevalence of a range of seizure precipitants in DS. Our results underscore elevated body temperature as an important seizure precipitant, whether caused by fever, warm bath, ambient warmth, or physical exercise. Knowledge of these seizure precipitants may improve preventive strategies in the otherwise difficult treatment of DS.     

Comparison between febrile and afebrile seizures associated with mild rotavirus gastroenteritis

PurposeWe aimed on identifying the differences of febrile and afebrile seizures associated with mild rotavirus gastroenteritis (RVGE) in the pediatric population.MethodMedical charts of pediatric patients who had been admitted between July 1999 and June 2011 due to RVGE were retrospectively reviewed. Subjects were ultimately divided into three groups; ‘no seizure’ (NS: patients without seizure), ‘febrile seizure’ (FS: patients with fever during seizure), ‘afebrile seizure’ (AFS: patients without fever during seizure). Comparisons between groups were carried out on demographic and clinical characteristics, laboratory test results, electroencephalogram findings, brain magnetic resonance imaging findings, antiepileptic treatment, and prognosis.ResultsAmong the 755 subjects who had been admitted due to mild rotavirus enteritis, 696 (90.3%) did not have any seizures, 17 (2.2%) had febrile seizures, 42 (5.5%) had afebrile seizures. The duration of gastrointestinal symptoms before the onset of seizures were significantly shorter in the FS group compared to the AFS group (1.3 ± 0.8 vs. 2.8 ± 1.0 days; p < 0.0001). A single seizure attack was significantly higher in the AFS group (3.0 ± 1.6 vs. 1.7 ± 1.0 episodes; p = 0.0003), and the frequency of seizures that were of focal type with or without secondary generalization were significantly higher in the AFS group (33.3% vs. 6.0%; p = 0.0139). All patients among the FS and AFS group had not received further antiepileptic treatment after discharge, and none developed epilepsy during follow up period.ConclusionDespite some differences in seizure characteristics, both febrile and afebrile seizures associated with mild RVGE were mostly benign with a favorable prognosis.     

Acute postoperative seizures and long-term outcome following pediatric epilepsy surgery

PurposeAcute post-operative seizures (APOS) after epilepsy surgery, previously believed to be benign, are increasingly associated with poor long-term prognosis. Prior literature has focused primarily on adult temporal lobe epilepsy. This retrospective study aimed to identify the prevalence, prognostic significance and risk factors for APOS in pediatric epilepsy surgery at a single center.MethodRetrospective chart review of all children aged 0–21 years undergoing resective surgery for epilepsy between 2009 and 2012 at a single center. APOS were defined as seizures within 30 days of resection. Surgical outcome was determined, using a minimum of 12 months postoperative follow-up for inclusion.ResultsAPOS, defined as a seizure within 30 days of resection, were identified in 50/112 (44%) of patients. APOS were a significant predictor of poor postoperative seizure outcome (ILAE 4–6); only 26% of those with APOS had a good outcome (ILAE 1–3), compared to 76% without APOS. Timing of postoperative seizure was not correlated with outcome. Most (54%) with APOS and good outcome had continued seizures between 14-30 days postoperatively. Patients with APOS after temporal (p = 0.05) and extratemporal (p < 0.001) resections had a significantly worse prognosis. APOS after hemispherectomy were not associated with a worse prognosis (p = 0.22). Key risk factors for APOS include lack of ictal EEG lateralization to operated hemisphere/side of MRI abnormality.ConclusionThis study shows an association between APOS and poor outcome in both temporal and extratemporal pediatric epilepsy surgery. Findings support the expansion of APOS duration to 30 days.     

Clinical features of the pre-ictal state: Mood changes and premonitory symptoms

Identifying the pre-ictal state clinically would improve our understanding of seizure onset and suggest opportunities for new treatments. In our previous paper-diary study, increased stress and less sleep predicted seizures. Utilizing electronic diaries, we expanded this investigation. Variables were identified by their association with subsequent seizure using logit-normal random effects models fit by maximum likelihood. Nineteen subjects with localization-related epilepsy kept e-diaries for 12–14 weeks and reported 244 eligible seizures. In univariate models, several mood items and ten premonitory features were associated with increased odds of seizure over 12 h. In multivariate models, a 10-point improvement in total mood decreased seizure risk by 25% (OR 0.75, CI 0.61–0.91, p = 004) while each additional significant premonitory feature increased seizure risk by nearly 25% (OR 1.24, CI 1.13–1.35, p < 001) over 12 h. Pre-ictal changes in mood and premonitory features may predict seizure occurrence and suggest a role for behavioral intervention and pre-emptive therapy in epilepsy.     

Is reoperation an option for patients with temporal lobe epilepsy after failure of surgery?

PurposeEpilepsy surgery is the most efficacious therapeutic modality for patients with medically refractory focal epilepsies, but surgical failures remain a challenge to the epilepsy treatment team. The aim of present study was to evaluate the postoperative outcome of patients who underwent reoperation after a failed epilepsy surgery on the temporal lobe.MethodsWe systematically analyzed the results of comprehensive preoperative evaluations before the first surgery, and before and after reoperation in 17 patients with drug resistant temporal lobe epilepsies.ResultsOverall, 13 of 17 patients (76.5%) improved after reoperation: five patients (29.4%) were completely seizure free after reoperation (median duration 60 months, range 12–72); six patients (35.3%) were seizure free at least 12 month before observation points (median duration 120.5 months, range 35–155) and two patients (11.8%) had a decrease in seizure frequency. Four patients (23.5%) remained unchanged with respect to seizure frequency and severity. There was no correlation between the improvement in seizure outcome after reoperation and other clinical data except of the history of traumatic brain injury (TBI). The patients who had no history of TBI improved after reoperation, compared to patients with TBI (p = 0.044). The postoperative seizure outcome of patients with incongruent Video-EEG results before the first surgery (p = 0.116) and before reoperation (p = 0.622) was not poorer compared to patients with congruent Video-EEG results.ConclusionsReoperation can considerably improve the operative outcome of the first failed epilepsy surgery in patients with drug resistant temporal lobe epilepsies. Epilepsy centres should be encouraged to report the results of failed epilepsy surgeries.     

Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data

ObjectiveDrug-resistant epilepsy is a devastating disorder associated with diminished quality of life (QOL). Surgical resection leads to seizure freedom and improved QOL in many epilepsy patients, but not all individuals are candidates for resection. In these cases, neuromodulation-based therapies such as vagus nerve stimulation (VNS) are often used, but most VNS studies focus exclusively on reduction of seizure frequency. QOL changes and predictors with VNS remain poorly understood.MethodUsing the VNS Therapy Patient Outcome Registry, we examined 7 metrics related to QOL after VNS for epilepsy in over 5000 patients (including over 3000 with ≥ 12 months follow-up), as subjectively assessed by treating physicians. Trends and predictors of QOL changes were examined and related to post-operative seizure outcome and likelihood of VNS generator replacement.ResultsAfter VNS therapy, physicians reported patient improvement in alertness (58–63%, range over follow-up period), post-ictal state (55–62%), cluster seizures (48–56%), mood change (43–49%), verbal communication (38–45%), school/professional achievements (29–39%), and memory (29–38%). Predictors of net QOL improvement included shorter time to implant (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1–1.6), generalized seizure type (OR, 1.2; 95% CI, 1.0–1.4), female gender (OR, 1.2; 95% CI, 1.0–1.4), and Caucasian ethnicity (OR, 1.3; 95% CI, 1.0–1.5). No significant trends were observed over time. Patients with net QOL improvement were more likely to have favorable seizure outcomes (chi square [χ²] = 148.1, p < 0.001) and more likely to undergo VNS generator replacement (χ² = 68.9, p < 0.001) than those with worsened/unchanged QOL.SignificanceVNS for drug-resistant epilepsy is associated with improvement on various QOL metrics subjectively rated by physicians. QOL improvement is associated with favorable seizure outcome and a higher likelihood of generator replacement, suggesting satisfaction with therapy. It is important to consider QOL metrics in neuromodulation for epilepsy, given the deleterious effects of seizures on patient QOL.     

Risk factors for valproic acid resistance in childhood absence epilepsy

AimsValproic acid (VPA) is reported to be effective for the control of absence seizures in 75% of children. The aim of this study was to determine the clinical and socio-demographic factors associated with VPA response in newly diagnosed childhood absence epilepsy (CAE) and to determine if these factors also influence the chances of achieving long-term seizure freedom.MethodsMedical charts of 180 children with CAE were retrospectively reviewed. Clinical, electroencephalographic and imaging findings were recorded to correlate with complete VPA response and long-term epilepsy outcome. Factors associated with non-responsiveness were identified individually and in a multivariable logistic regression analysis.ResultsTreatment was successful in 112 (58.3%) children. More children that were non-responsive to VPA experienced generalized tonic clonic seizures (GTCS) (33.8% vs. 13.4% for responders; p = 0.001) and 52.9% had a pre-treatment seizure frequency greater than 10/day (vs. 27.0% for responders; p < 0.001). Finally, responders were older at time of diagnosis versus non-responders (p = 0.001). Absence of long-term seizure freedom was linked to the presence of GTCS, the absence of initial response and the need for multiple AEDs to control seizures.InterpretationOur results suggest that clinical phenotypes are associated with reduced response rates to VPA. This should be taken into account when counselling families of children with newly diagnosed absence epilepsy.     

Marijuana use in adults admitted to a Canadian epilepsy monitoring unit

ObjectivesEpidemiologic evidence supporting antiseizure properties of cannabis is limited and controversial. We determined the prevalence of marijuana use and its perceived effects in patients with and without epilepsy.MethodsInformation was collected over 14 months from consecutive adult patients admitted to an epilepsy monitoring unit using a 27-item anonymous questionnaire. Patients with cognitive impairment unable to understand the questions or give informed consent and readmissions were not recruited. Subjects were divided into 4 groups, those with epileptic seizures, those with psychogenic nonepileptic seizures (PNES), those with both epileptic and PNES, and those with other nonepileptic events. Patients with exclusively epileptic seizures were compared with those with exclusively PNES.ResultsFrom 310 patients, 18 undiagnosed cases were excluded leaving a cohort of 292 patients with median age 35 (range: 27–49) years; 57.2% female. Epilepsy was documented in 190 (65.1%), PNES in 64 (21.9%), and both types of seizures in 26 (8.9%). Median duration of seizure disorder was longer (2 [1–9] vs. 13 [5.7–25] years; p < 0.001) and seizure frequency lower (daily or weekly in 62.3% vs. 44.9%; p = 0.03) in patients with epilepsy compared with those in patients with PNES. Overall, 166 (57%) had tried marijuana, and 36.2% used it over the past year. Utilization was 57.1% in sole epilepsy and 64.1% in sole PNES, but daily use was more likely in epilepsy (59% vs. 33.3%). Estimated mean dose was 1 g/day. Marijuana use was associated with tobacco smoking (p < 0.001) but not alcohol use. Eight patients used other street drugs. Improvement in seizures was perceived by 84% in those with epilepsy and 72.7% in those with PNES. In the 2 groups, stress was decreased in 84.9% and 88%, sleep improved in 77.3% and 88%, and memory/concentration was better in 32% and 28%, respectively. Antiepileptic drug side effects were decreased in 53.2% of marijuana users. Perceived effect on epileptic seizures correlated with effect on stress (r = 0.35, p = 0.004). Adverse effects of marijuana were mild and reported in 30.7% but included possible seizure precipitation in 5 patients with epilepsy.SignificancePatients with uncontrolled epilepsy or nonepileptic events had a high rate of marijuana use with associated perceived improvements in seizure control, stress, sleep, and drug side effects. Stress reduction may contribute to the perceived impact of marijuana on seizures and nonepileptic events in adults.     

Seizure-related injuries in children and adolescents with epilepsy

BackgroundChildren with epilepsy are reported to be at a greater risk of injuries compared with their peers who do not have epilepsy.ObjectivesWe set out to determine the frequency and pattern of seizure-related injuries in children with epilepsy seen at the University College Hospital (UCH), Ibadan, Nigeria.MethodsConsecutive cases of epilepsy seen at the pediatric neurology clinic of the UCH, Ibadan over a period of 6 months were evaluated for injuries in the preceding 12 months using a structured questionnaire. These were compared with age- and sex-matched controls.ResultsA total of 125 children with epilepsy and 125 age- and sex-matched controls were studied. Injuries occurred more frequently in children with epilepsy than in their peers (p = 0.01, OR 1.935, 95% CI 1.142–3.280). Epilepsy was generalized in 80 (64.0%), and localization-related in 45 (36.0%). Idiopathic epilepsy accounted for 74 (59.2%), and the remaining 51 (40.8%) had remote symptomatic epilepsy. Fifty-seven (45.6%) children had suffered seizure-related injuries with multiple injuries in 31 (24.8%). The most frequent were skin/soft tissue lacerations (26.4%), injuries to the tongue and soft tissues of the mouth (19.2%), minor head injuries (15.2%), and dental injuries with tooth loss (8.0%). There was a statistically significant association between seizure frequency and seizure-related injuries (p = 0.002). Children on polytherapy had a significantly higher frequency of seizure-related injuries (p < 0.001).ConclusionEpilepsy is a major risk factor for injuries in childhood. High seizure frequency increases the risk of multiple injuries in children with epilepsy.     

Impact of planning of pregnancy in women with epilepsy on seizure control during pregnancy and on maternal and neonatal outcomes

PurposeTo investigate whether planning of pregnancy in women with epilepsy affects seizure control during pregnancy and to compare the maternal and neonatal outcomes in planned and unplanned pregnancies.MethodsThis was a retrospective cohort study of 153 pregnant women with epilepsy who were treated at the University of Tsukuba Hospital and Hokkaido University Hospital between 2003 and 2011. Twenty-one pregnancies were excluded due to insufficient data. Data of patients followed by neurologists during their planned pregnancies (planned-pregnancy group, n = 51) were compared to those of patients referred to neurologists after conception for managing epilepsy during pregnancy (unplanned-pregnancy group, n = 81). The treatment profile for epilepsy, seizure control, and maternal and neonatal outcomes in both groups were compared using Chi-square test or Fisher's exact test and Mann–Whitney U test.ResultsCompared to the unplanned-pregnancy group, the planned-pregnancy group showed a significantly greater proportion of patients receiving monotherapy with antiepileptic drugs (80% vs. 61%: planned vs. unplanned, P = 0.049) and those not requiring valproic acid (77% vs. 56%, P = 0.031). Furthermore, the frequency of epileptic seizures (16% vs. 35%, P = 0.018) and changes in antiepileptic drugs (24% vs. 41%, P = 0.042) were significantly lower in the planned-pregnancy group than in the unplanned-pregnancy group. No significant intergroup differences were noted in the obstetric complications and neonatal outcomes, including congenital malformations.ConclusionFor women with epilepsy, planning of pregnancy is associated with good seizure control during pregnancy and less fetal exposure to antiepileptic drugs.     

The impact of stereotactic laser ablation at a typical epilepsy center

PurposeStereotactic laser ablation (SLA) is a novel form of epilepsy surgery for patients with drug-resistant focal epilepsy. We evaluated one hundred consecutive surgeries performed for patients with epilepsy to address the impact of SLA on our therapeutic approach, as well as patient outcomes.MethodsA retrospective, single center analysis of the last one hundred neurosurgeries for epilepsy was performed from 2013 to 2015. Demographics, surgical procedures, and postoperative measures were assessed up to 5 years to compare the effect of SLA on outcome. Confidence intervals (CI) and comparative tests of proportions compared outcomes for SLA and resective surgery. Procedural categorical comparison used Chi-square and Kaplan–Meier curves. Student t-test was utilized for single variables such as age at procedure and seizure onset.ResultsOne hundred surgeries for epilepsy yielded thirty-three SLAs and twenty-one resections with a mean of 21.7-month and 21.3-month follow-up, respectively. The temporal lobe was the most common target for SLA (92.6%) and resection (75%). A discrete lesion was present on brain magnetic resonance imaging (MRI) in 27/32 (84.4%) of SLA patients compared with 7/20 (35%) of resection patients with a normal MRI. Overall, 55–60% of patients became seizure-free (SF). Four of five patients with initial failure to SLA became SF with subsequent resection surgery. Complications were more frequent with resection although SF outcomes did not differ (Chi square; p = 0.79). Stereotactic laser ablation patients were older than those with resections (47.0 years vs. 35.4 years, p = 0.001). The mean length of hospitalization prior to discharge was shorter for SLA (1.18 days) compared with open resection (3.43 days; SD: 3.16 days) (p = 0.0002).ConclusionWe now use SLA as a first line therapy at our center in patients with lesional temporal lobe epilepsy (TLE) before resection. Seizure-free outcome with SLA and resection was similar but with a shorter length of stay. Long-term follow-up is recommended to determine sustained SF status from SLA.     

Initial response to antiepileptic drugs in patients with newly diagnosed epilepsy

This study aimed to identify factors predicting the response to antiepileptic drugs in patients with newly diagnosed epilepsy. We prospectively studied 176 patients with newly diagnosed epilepsy. Patients were included if they had a history of two or more clinically definite unprovoked seizures, or had a definite epileptic focus on MRI or epileptiform discharges on electroencephalography if they had suffered only one seizure. The primary endpoint was seizure freedom during the initial 6 months of antiepileptic drug treatment. The secondary endpoint was the time to the first seizure during the maintenance period of antiepileptic drug treatment. A total of 100 patients were included, and seizure freedom for 6 months was achieved in 73 patients. The response to antiepileptic drugs was significantly lower in patients with early age at seizure onset (⩽16 versus >16 years old, odds ratio = 4; 95% confidence interval [CI] 1.5–12.9; relative risk = 1.4; 95% CI 1.1–1.8). In addition, the time to the first seizure during the maintenance period was significantly earlier in patients with age at seizure onset ⩽16 years compared with those with age at seizure onset >16 years on the Kaplan–Meier survival analysis (p = 0.011). Early age at seizure onset is an important factor influencing the response to antiepileptic drugs in patients with newly diagnosed epilepsy.     

Comorbidities and risk factors associated with newly diagnosed epilepsy in the U.S. pediatric population

Neurobehavioral comorbidities can be related to underlying etiology of epilepsy, epilepsy itself, and adverse effects of antiepileptic drugs. We examined the relationship between neurobehavioral comorbidities and putative risk factors for epilepsy in children with newly diagnosed epilepsy. We conducted a retrospective analysis of children aged ≤ 18 years in 50 states and the District of Columbia, using the Truven Health MarketScan® commercial claims and encounters database from January 1, 2009 to December 31, 2013. The eligible study cohort was continuously enrolled throughout 2013 as well as enrolled for any days during a baseline period of at least the prior 2 years. Newly diagnosed cases of epilepsy were defined by International Classification of Diseases, Ninth Revision, Clinical Modification-coded diagnoses of epilepsy or recurrent seizures and evidence of prescribed antiepileptic drugs during 2013, when neither seizure codes nor seizure medication claims were recorded during baseline periods. Twelve neurobehavioral comorbidities and eleven putative risk factors for epilepsy were measured. More than 6 million children were analyzed (male, 51%; mean age, 8.8 years). A total of 7654 children were identified as having newly diagnosed epilepsy (125 per 100,000, 99% CI = 122–129). Neurobehavioral comorbidities were more prevalent in children with epilepsy than children without epilepsy (60%, 99% CI = 58.1–61.0 vs. 23%, CI = 23.1–23.2). Children with epilepsy were far more likely to have multiple comorbidities (36%, 99% CI = 34.3–37.1) than those without epilepsy (8%, 99% CI = 7.45–7.51, P < 0.001). Preexisting putative risk factors for epilepsy were detected in 28% (99% CI = 26.9–29.6) of children with epilepsy. After controlling for demographics, neurobehavioral comorbidities, family history of epilepsy, and other risk factors than primary interest, neonatal seizures had the strongest independent association with the development of epilepsy (OR = 29.8, 99% CI = 23.7–37.3, P < 0.001). Compared with children with risk factors but no epilepsy, those with both epilepsy and risk factors were more likely to have intellectual disabilities (OR = 13.4, 99% CI = 11.9–15.0, P < 0.001). The epilepsy and intellectual disabilities could share the common pathophysiology in the neuronal network.